N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation

Xiang Zhou; Ella J Born; Cheryl Allen; Sarah A Holstein; David F Wiemer

doi:10.1016/j.bmcl.2015.04.021

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N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation

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N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation

Xiang Zhou, Ella J Born, Cheryl Allen, Sarah A Holstein and David F Wiemer

Bioorganic & medicinal chemistry letters, Vol.25(11), pp.2331-2334

06/01/2015

DOI: 10.1016/j.bmcl.2015.04.021

PMCID: PMC4462192

PMID: 25935643

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Abstract

[Display omitted] The N-oxide derivatives of [2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid (or PEHPC) and [2-(3-pyridinyl)-1-ethylidene-1,1-phosphonocarboxylic acid (or PEPC) have been prepared and evaluated for their activity against several enzymes which utilize isoprenoids. The parent pyridines are known inhibitors of GGTase II, but the N-oxide derivatives show no improvement in biological activity in assays with the isolated enzyme. However, the PEHPC N-oxide did induce significant accumulation of intracellular light chain in myeloma cells, consistent with inhibition of Rab geranylgeranylation.

Apoptosis

Bioassay

GGTase II

Rab GGTase

Myeloma

Pyridyl N-oxides

Details

Title: Subtitle: N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation
Creators: Xiang Zhou - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA
Ella J Born - Department of Internal Medicine, University of Iowa, Iowa City, IA 52242-1294, USA
Cheryl Allen - Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
Sarah A Holstein - Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
David F Wiemer - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA
Resource Type: Journal article
Publication Details: Bioorganic & medicinal chemistry letters, Vol.25(11), pp.2331-2334
DOI: 10.1016/j.bmcl.2015.04.021
PMID: 25935643
PMCID: PMC4462192
NLM abbreviation: Bioorg Med Chem Lett
ISSN: 0960-894X
eISSN: 1464-3405
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100000002, name: NIH, award: R01CA-172070
Language: English
Date published: 06/01/2015
Academic Unit: Neuroscience and Pharmacology; Chemistry
Record Identifier: 9983986098102771

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